tbuckley/cabot-search huggingface dataset:
How do income changes impact on mental health and wellbeing for working-age adults? A systematic review and meta-analysis
Authors: Rachel M Thomson, Erik Igelström, Amrit Kaur Purba, Michal Shimonovich, Hilary Thomson, Gerry McCartney, Aaron Reeves, Alastair Leyland, Anna Pearce, S Vittal Katikireddi
Journal: The Lancet Public Health (2022)

BackgroundLower incomes are associated with poorer mental health and wellbeing, but the extent to which income has a causal effect is debated. We aimed to synthesise evidence from studies measuring the impact of changes in individual and household income on mental health and wellbeing outcomes in working-age adults (aged 16–64 years).MethodsFor this systematic review and meta-analysis, we searched MEDLINE, Embase, Web of Science, PsycINFO, ASSIA, EconLit, and RePEc on Feb 5, 2020, for randomised controlled trials (RCTs) and quantitative non-randomised studies. We had no date limits for our search. We included English-language studies measuring effects of individual or household income change on any mental health or wellbeing outcome. We used Cochrane risk of bias (RoB) tools. We conducted three-level random-effects meta-analyses, and explored heterogeneity using meta-regression and stratified analyses. Synthesis without meta-analysis was based on effect direction. Critical RoB studies were excluded from primary analyses. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). This study is registered with PROSPERO, CRD42020168379.FindingsOf 16 521 citations screened, 136 were narratively synthesised (12·5% RCTs) and 86 meta-analysed. RoB was high: 30·1% were rated critical and 47·1% serious or high. A binary income increase lifting individuals out of poverty was associated with 0·13 SD improvement in mental health measures (95% CI 0·07 to 0·20; n=42 128; 18 studies), considerably larger than other income increases (0·01 SD improvement, 0·002 to 0·019; n=216 509, 14 studies). For wellbeing, increases out of poverty were associated with 0·38 SD improvement (0·09 to 0·66; n=101 350, 8 studies) versus 0·16 for other income increases (0·07 to 0·25; n=62 619, 11 studies). Income decreases from any source were associated with 0·21 SD worsening of mental health measures (–0·30 to –0·13; n=227 804, 11 studies). Effect sizes were larger in low-income and middle-income settings and in higher RoB studies. Heterogeneity was high (I2=79–87%). GRADE certainty was low or very low.InterpretationIncome changes probably impact mental health, particularly where they move individuals out of poverty, although effect sizes are modest and certainty low. Effects are larger for wellbeing outcomes, and potentially for income losses. To best support population mental health, welfare policies need to reach the most socioeconomically disadvantaged.FundingWellcome Trust, Medical Research Council, Chief Scientist Office, and European Research Council.
Surgical management and oncologic outcomes for local recurrence of renal cell carcinoma after radical nephrectomy
Authors: J. Huang, Y. Wang, C. Zhang, X. Hu, P. Wang, G. Shi, L. Dong, J. Zhang, W. Kong, Y. Chen, D. Ye, D. Xia, J. Guo, W. Xue, Y. Huang, Z. He
Journal: European Urology (2022)
Neoadjuvant combined chemotherapy and immunotherapy for upper tract urothelial carcinoma: Preliminary results of a phase II study
Authors: X. Bi, J. Shou, A. Zhou, W. Zhang, C. Cao, L. Lu, L. Wen, Y. Guan, H. Shi, Z. Xiao, Z. Jiang, Y. Sun, S. Zheng, J. Zhang
Journal: European Urology (2022)
Mortality and prognostic factors in hospitalized COVID-19 patients with cancer: An analysis from a large healthcare system in the United States.
Authors: Meri Tarockoff, Luis E. Raez, Carlos Carracedo Uribe, Jianli Niu, Candice Sareli, Nithya Sundararaman, Jayme Ion, Paula Eckardt, Atif Mahmoud Hussein
Journal: Journal of Clinical Oncology (2022)

e24063 Background: Coronavirus 19 (COVID-19) is a severe global pandemic and a public health challenge. Patients with COVID-19 and cancer are at an increased risk of poor clinical outcomes. Data is lacking in evaluating outcomes in patients with different cancers, races and ages; particularly in Florida with high proportion of elderly and the largest racial/ethnic disparities. We evaluated the in-hospital mortality of COVID-19 positive cancer patients. Methods: We used retrospective data of COVID-19 patients hospitalized at the Memorial Healthcare System between March 1, 2020 and January 18, 2021. Over 4,870 patients with COVID-19 were evaluated, of which 265 (5.4%) had cancer. The primary endpoint was in-hospital mortality in patients with cancer and COVID-19. Mortality was analyzed in COVID-19 patients with/without a cancer history. We used descriptive statistics to synthesize outcomes and characteristics from the study population. Univariate and multivariate logistic analysis were performed to define baseline clinical characteristics potentially associated with mortality in cancer patients with COVID-19. Results: 4,870 patients with COVID-19 were evaluated and 265 had malignancy. The study included all different races including Non-Hispanic Whites (NHW) 816 (16.8%), Hispanics 2,271 (46.6%), African-Americans (AA) 1,534 (31.5%) and other minorities 248 (5.1%). Of cancer patients, 24.1% NHW, 43% Hispanic, 28.7% AA and 4.2% other minorities. Amongst races, NHW with cancer accounted for the highest number of COVID-related deaths representing 37.5%, while Hispanics and AA accounted for 18.4% and 19.7% respectfully. Amid cancer subtypes, 24.6% of hematological cancers resulted in mortality and 23.5% of solid cancers resulted in mortality, but no statistical significance was seen. Additionally, after adjusting for age, gender, and race, cancer was linked to an increased in-hospital mortality. Lastly, older age (&gt; 65), elevated creatinine levels (Cr) and elevated C-reactive protein (CRP) were associated with increased risk of death. Conclusions: Patients with COVID-19 and cancer had worse outcomes. Cancer subtypes included hematological and solid cancers, with similar in-hospital mortalities. Although NHW were the smallest group, they had the highest rate of in-hospital deaths amongst cancer patients with COVID-19, in comparison to Hispanics, the largest group in the study, had the least amount of in-hospital deaths. Additionally, factors such as advanced age, elevated Cr and CRP were associated with increased risk of COVID-related deaths. The findings indicate the need for close surveillance and monitoring of these patients as they are more likely to have complications such as mortality from COVID-19.
Deficiency in the zinc transporter ZIP8 impairs epithelia renewal and enhances lung fibrosis
Authors: Paul S. Foster, Hock L. Tay, Brian G. Oliver
Journal: Journal of Clinical Investigation (2022)

Although aging and lung injury are linked to the development of idiopathic pulmonary fibrosis (IPF), the underlying pathognomonic processes predisposing to fibrotic lesions remain largely unknown. A deficiency in the ability of type 2 alveolar epithelial cell (AEC2) progenitors to regenerate and repair the epithelia has been proposed as a critical factor. In this issue of the JCI, Liang et al. identify a deficiency in the zinc transporter SLC39A8 (ZIP8) in AEC2s and in the subsequent activation of the sirtuin SIRT1 that predisposes to decreased AEC2 renewal capacity and enhanced lung fibrosis in both IPF and aging lungs. Interestingly, the authors demonstrate the efficacy of modulating dietary zinc levels, suggesting the need for clinical trials to evaluate the therapeutic potential of dietary supplementation and the development of pharmacological modulation of the Zn/ZIP8/SIRT1 axis for treatment.
Tirzepatide Once Weekly for the Treatment of Obesity
Authors: Ania M. Jastreboff, Louis J. Aronne, Nadia N. Ahmad, Sean Wharton, Lisa Connery, Breno Alves, Arihiro Kiyosue, Shuyu Zhang, Bing Liu, Mathijs C. Bunck, Adam Stefanski
Journal: New England Journal of Medicine (2022)

Obesity is a chronic disease that results in substantial global morbidity and mortality. The efficacy and safety of tirzepatide, a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, in people with obesity are not known.
Evaluation of the quality of screening for hypertension
Authors: ZH Bekbergenova, G Derbissalina, A Umbetzhanova, SH Batarbekova, A Masharipova, G Mauletbayeva, D Akhmetova, E Kelimberdiyeva
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: None. Main funding source(s): - Background/Introduction Hypertension is one of the most common causes of myocardial infarction and stroke in the Republic of Kazakhstan (RK). In RK, screening for hypertension is performed with 40-years of age. Purpose To assess the quality of the screening for hypertension. Methods A survey of 354 patients with hypertension identified at screening was carried out. Results The average age of patients is 54 years [Q1-Q3: 50-54], of which 36.2% are men, 63.8% are women. In 66.7% of patients, heredity is burdened. According to the analysis of medical records, 117 (33.1%) patients smoke, while polling the same patients, 175 (49.4%) people smoke, which is 16.3% higher. According to the analysis, 38 (10.7%) patients drink, when we interviewed the same patients, 62 (17.5%) people drink, which is 6.8% higher. According to the analysis, 219 (61.9%) patients perform daily physical activity, according to our data, 111 (31.4%) people, which is 30.5% lower. Middle systolic blood pressure is 140 [Q1-Q3: 130-140] mm Hg. Most of the respondents have varying degrees of obesity. The average body mass index is 31.86 [Q1-Q3: 29.4-31.86]. The average waist is 95 [Q1-Q3: 92-95]. Mean values of total cholesterol. 5.8 [Q1-Q3: 5.6-5.8]. During the electrocardiographic study, changes were identified in 69 patients (32 women, 37 men). Conclusion (s) During the initial questionnaire survey and clinical examination of patients with arterial hypertension at screening in 2015 and comparison with retrospective data, it became clear that such risk factors as tobacco smoking, alcohol consumption and daily physical activity were unreliable. Unfortunately, our work also has limitations and may be subject to subjective error, for example, we were unable to establish contact with the patient and a trusting relationship with the patient, or memory errors.
Mitoxantrone hydrochloride liposome injection in the treatment of recurrent/metastatic head and neck cancers: A multicenter, open-label, single-arm, phase Ⅰb study.
Authors: Hang Yang, Xicheng Wang, Hong Zhang, Jiyong Peng, Weidong Li, Yanyan Liu, Jianbing Hu, Hui Zhou, Bing Zhang, Jixiang Liu, Shunhuan Lin, Hao Luo, Jie Hu, Zhiming Li
Journal: Journal of Clinical Oncology (2022)

e18028 Background: Mitoxantrone is an anthraquinone antibiotic antitumor agent, and mitoxantrone hydrochloride liposomes have been approved for the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL) in China. The current study aimed to evaluate the safety and efficacy of mitoxantrone hydrochloride liposome in patients (pts) with recurrent/metastatic head and neck cancers. Methods: This study is a multicenter, open-label, single-arm, phase Ⅰb study. The pts with histologically confirmed diagnosis of head and neck squamous cell carcinoma (including nasopharyngeal carcinoma) were enrolled. Mitoxantrone hydrochloride liposome was administered at 20 mg/m 2 by an intravenous infusion, every 21 days (q3w, 1 cycle) until disease progression, intolerable toxic reaction, death, or withdrawal by investigator or patient decision (a maximum of 8 cycles). The primary objective was to determine the safety of mitoxantrone hydrochloride liposome. Secondary objective was to assess the efficacy of mitoxantrone hydrochloride liposome in the treatment of recurrent/metastatic head and neck squamous cell carcinoma. Efficacy assessment was performed every 2 cycles after dosing as per RECIST v1.1. Results: From July 8, 2021 through November 5, 2021, 34 pts with median age of 48 years (range 20-69 years) were enrolled, including 23 with nasopharyngeal cancer and 11 with non-nasopharyngeal cancer (5 with tongue cancer, 2 with hypopharynx, 2 with tonsil cancer, and 1 each with larynx and gum cancer). The most common treatment-emergent adverse events (TEAEs) were white blood cell decreased (41.2%), anemia (41.2%) and lymphocyte count decreased (29.4%). TEAEs were generally Grade (G) 1-2; 13 pts reported G3 TEAE. The summary of all-grade TEAEs (≥ 10%) are shown in the table below. Nineteen pts had undergone at least 1 efficacy evaluation (including 18 pts with nasopharyngeal cancer and 1 with non-nasopharyngeal cancer). The overall objective response rate (ORR) was 42.1% (8/19) and disease control rate (DCR) was 78.9% (15/19). ORR for nasopharyngeal cancer was 38.9% (7/18) and DCR was 77.8% (14/18). One case of hypopharyngeal cancer was evaluated as partial remission (PR). Conclusions: The preliminary data of mitoxantrone hydrochloride liposome has showed manageable safety and evidence of efficacy in pts with recurrent/metastatic head and neck squamous cell carcinoma. An expanded sample size is still needed for further validation in the future study. Clinical trial information: NCT04902027. [Table: see text]
Prospective validation of the ROL system in substaging pT1 high-grade bladder cancer: A confirmatory progression risk analysis to ease decision making
Authors: M. Valeri, R. Contieri, V. Fasulo, M. Cieri, G.M. Elefante, C. De Carlo, C. Saitta, A. Gobbo, P.P. Avolio, M. Lazzeri, G. Taverna, L.M. Terracciano, R. Hurle, P. Colombo
Journal: European Urology (2022)
Ribociclib-induced acute kidney injury: Uncover the MONALEESA’s dark face.
Authors: Maissoune Hajir, Ramiz Ahmad Abu-Hijlih, Areej Abu Sheikha, Kholoud Alqasem, Hikmat Abdel-Razeq
Journal: Journal of Clinical Oncology (2022)

1063 Background: The phase-3 MONALEESA-2,-3 and -7 randomized trials showed improved progression-free survival (PFS) and overall survival (OS) with the addition of cyclin D-cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib to endocrine therapy in women with advanced-stage breast cancer. However, ribociclib induced acute renal injury is not recognized in these studies. In this report, we explore ribociclib-induced acute kidney injury (AKI) in breast cancer patients receiving ribociclib. Methods: We performed a retrospective chart review of all breast cancer patients who received ribociclib at our institution between April 2019 and September 2021. Patients and disease characteristics were collected, details of creatinine kinetics in relation to administration of ribociclib and other nephrotoxic drugs were obtained. Acute kidney injury grades (AKI-KDIGO classification) were captured. Results: 145 females, median age 60.0 years, all with advanced-stage breast cancer treated with aromatase inhibitors (AI) or fulvestrant plus ribociclib were reviewed. A total of 26 (17.9%) patients developed AKI; 3 were grade-I, 21 grade-II and 2 were grade-III. Rate of AKI was significantly higher (n = 15, 48.4%) among 31 patients on other concomitant nephrotoxic drugs, compared to 11 (9.6%) of 114 other patients, p = 0.001. Nephrotoxic drugs include non-steroidal anti-inflammatory (38%), metformin (30%), angiotensin-II receptor blockers (26%), and angiotensin-converting enzyme inhibitors (11%). Median time to develop AKI was 54 (range, 21-168) days, while the median time for creatinine recovery was 5 (range, 4-7) days after holding the drugs. Average creatinine increment for affected patients was 2.28 times the baseline level. Time to AKI was shorter, but not statistically significant, among patients on nephrotoxic drugs and recovery was faster after stopping these drugs (Table). Conclusions: Ribociclib-induced AKI is not uncommon and not adequately addressed. Though reversable in majority of patients, some patients may develop grade-III AKI or require treatment interruption. Nephrotoxic medications seem to significantly enhance ribociclib-associated renal injury. Withhold these medications with periodical assessment by nephrologist is strongly recommended in these patients. Larger studies are warranted to validate our findings. [Table: see text]
Financial impact of biosimilar adoption in the oncology care model for the U.S. Oncology Network.
Authors: Lalan S. Wilfong, Puneeth Indurlal, Kaci Dominguez, Jody S. Garey, Josh Howell, Stuart Staggs, Marcus A. Neubauer
Journal: Journal of Clinical Oncology (2022)

e18749 Background: Biosimilar adoption offers the potential to save significant cost while maintaining high quality of care. The Oncology Care Model (OCM) is structured to reward practices for decreasing total cost of care (TCOC) compared to historical baseline prices that are adjusted by a trend factor accounting for the rising cost of oncology care. Practices are rewarded for bending the cost curve by utilizing lower cost medications. Biosimilar options were introduced for 3 mainstay therapeutic classes in oncology, bevacizumab and trastuzumab in 2019, and rituximab in 2020. This led to a concerted approach for biosimilar adoption in The US Oncology Network (The Network) as an opportunity to reduce TCOC. Here we describe utilization and the financial impact of biosimilar adoption in The Network during OCM performance period 8 (PP8) which enrolled patients from 1/2/2020 to 7/1/2020. Methods: Claims data for the 14 US Oncology Network practices participating in the OCM were used to determine biosimilar utilization for bevacizumab, trastuzumab, and rituximab therapeutic classes. The impact of biosimilar utilization on TCOC was measured by comparing the cost of each dose of a biosimilar vs the estimated cost if the more expensive innovator agent had been used instead. Results: Biosimilar utilization increased for each therapeutic class from prior performance periods. Biosimilar use for bevacizumab was 0% in PP6, 5% in PP7 and 43% in PP8. For trastuzumab, utilization was 0% in PP6, 4% in PP7 and 33% in PP8. Rituximab biosimilar utilization was 0% in PP6, 2% in PP7 and 41% in PP8. We compared the actual cost of these three medications in our OCM claims in PP8 vs. the calculated cost based on Medicare reimbursement as ASP + 6% minus sequestration if the more expensive innovator drugs had been used entirely. The difference in the actual cost vs estimated cost led to a savings of $6.61 million by using the biosimilars over innovator drugs. Conclusions: The increased utilization of biosimilars in The Network generated significant savings in OCM. Continued adoption of biosimilars will increase savings to Medicare in the Oncology Care Model. We estimate that 100% Network adoption of these three biosimilars could save nearly 1.5% of the TCOC in our Network compared to continued use of innovator drugs.
OTHR-07. A new framework for missing value tolerant data integration
Authors: Hannah Voß, Simon Schlumbohm, Marcus Wurlitzer, Matthias Dottermusch, Philipp Neumann, Philip Barwikowski, Hartmut Schlüter, Christoph Krisp, Julia Neumann
Journal: Neuro-Oncology (2022)

Abstract Dataset integration is common practice to overcome limitations, e.g., in statistically underpowered omics datasets. This is of particular importance when analyzing rare tumor entities. However, combining datasets leads to the introduction of biases, so called 'batch effects', which are due to differences in quantification techniques, laboratory equipment or used tissue type. A common problem is the missing quantification for features like gene transcripts or proteins within a dataset. These missing values can appear at random in a given dataset and also get introduced by combination of multiple datasets. Currently, strategies beyond common normalization for batch effect reduction are either missing entirely or are unable to handle absence of data points and therefore rely on error-prone data imputation. We introduce a framework that enables batch effect adjustments for combined datasets while avoiding data loss by appropriately handling missing values without imputation. The underlying idea is based on a matrix dissection approach, adjusting common information from the integrated dataset under guarantee of sufficient data presence. The strategy is implemented within the R environment and linked with popular software stacks that are built on top of R. Successful data adjustment is exemplarily shown for proteomic data generated by different quantification approaches and LC-MS/MS instrumentation setups.
Real-world comparison of outcomes in the first line treatment of metastatic melanoma according to BRAF mutation status: Nivolumab and ipilimumab therapy vs. nivolumab monotherapy.
Authors: Avital Klein-Brill, Shlomit Amar-Farkash, Michael Jordan Fisch, Dvir Aran
Journal: Journal of Clinical Oncology (2022)

e21519 Background: In metastatic melanoma (MM) patients, nivolumab can be used as monotherapy or in combinations with ipilimumab. The combination therapy has been shown in a randomized clinical trial to provide survival benefit in BRAF mutant patients with an increased toxicity. Using real-world data, we evaluated the impact on overall survival and post-treatment hospitalizations of 1L nivo alone vs nivo+ipi. Methods: We performed a retrospective cohort study of 1L treatment of patients with MM between 1/2016 and 12/2020, utilizing administrative claims data from the Anthem Cancer Care Quality Program. Real-world overall survival (OS) was defined as time from diagnosis to death. A Cox model with inverse probability of treatment weighting (IPTW) was used to adjust for demographic and clinical features. Adjusted hazard ratios (aHR) were estimated using weighted Cox proportional hazards models. Results: Our cohort included 708 1L MM patients, of them 466 (66%) treated with nivo+ipi. There was no difference in BRAF status between the treatment groups. Patients treated with nivo+ipi were younger and had more evidence of brain and lung metastasis. Following adjustment, nivo treated had significant longer OS compared to the nivo+ipi treated (aHR: 1.73 (1.25-2.35), p = 8e-4). This difference mostly stems from increased mortality of the combo treated in the first 6 months. At 24-months, 58% of the combination therapy treated patients were alive compared to 74% in the monotherapy group (p = 0.0006). Survival benefit was only observed in BRAF WT patients. In V600E patients no survival difference was observed (aHR: 0.8 (0.4-1.6), p = 0.5). Patients treated with the combination therapy had 5-fold more hospitalizations during the first 90 days after the treatment start (46% vs 10%, p = 3e-22). Conclusions: Our retrospective cohort study demonstrated improved survival for the monotherapy in BRAF WT patients. Combination therapy was associated with significantly more treatment-related hospitalizations and deaths, mainly in the first 6 months. The increased early morbidity of the combo should be considered in treatment decision.[Table: see text]